Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tilorone hydrochloride (200 mg/kg) was administered intragastrically to inbred CBA mice. After 5, 18 and 48 hr the number of circulating leucocytes and peritoneal cells as well as the migration of unstimulated peritoneal cells, the blood corticosteroid level and interferon production were investigated. In spite of the considerable decrease of the number of mononuclear cells in the blood and polynuclear ones in the peritoneal exudate, the drug induced production of circulating interferon and stimulated its synthesis by peritoneal cells. The blood corticosteroid level and the mast cell count in the peritoneal cavity were significantly elevated, but the migration of peritoneal cells in antigen-free medium decreased.
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PMID:Effect of the interferon inducer tilorone in inbred CBA mice. 102 58

Over the years, many encouraging uncontrolled studies extolling treatments of SSc have appeared, but initial impressions were not corroborated when controlled trials were done. This article points out that certain recent studies have effectively ruled out the use of some specific therapies for the general treatment of systemic sclerosis. Thus, sufficient data has been generated to rule out the use of n-acetylcysteine, colchicine, chlorambucil, cyclofenil, and DMSO, at least in disease of longer duration. Ketanserin and prostaglandin infusions probably also belong in this group, as they affect only Raynaud's phenomenon. Angiotensin enzyme inhibitors, while probably life-saving in renal crises, do not seem to affect the underlying systemic sclerosis per se. Another group of drugs has only limited supportive data and await well-controlled trials to prove or disprove their effectiveness. These include: 5-fluorouracil, D-penicillamine, drugs affecting platelet function (dipyridamole), and para-aminobenzoic acid. There are a few treatments which have potential. Factor XIII has only limited data using controlled trials, but what does exist seems positive. Apheresis is encouraging, although the success of this treatment modality may be dependent upon a "combination" approach. Ongoing studies with gamma-interferon, photopheresis, and the mast cell stabilizer ketotifen appear exciting, and we await reports of their use in scleroderma. On another level, new insights into genomic alterations in skin fibroblasts and T-cell proto-oncogene expression have contributed to the understanding of the pathogenesis of this disease at the cellular level and new methods to measure change in disease will help gauge response to therapy. Thus, we look forward to more definitive treatment of SSc in the future.
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PMID:Treatment of generalized systemic sclerosis. 240 9

Keratinocytes are capable of releasing distinct immunomodulating cytokines such as epidermal cell-derived thymocyte activating factor (ETAF) and an epidermal cell-derived natural killer cell augmenting factor (ENKAF). The present study was performed to determine whether human keratinocytes also may secrete an interleukin 3 (IL-3)-like mediator and thereby participate in the regulation of mast cell activity in the skin. Supernatants of freshly isolated human epidermal cells (EC) and malignant keratinocyte cell lines (A 431, SCC) were tested for their capacity to induce the proliferation of IL-3-dependent cell lines 32 DCL and FDCP. Human epidermal cell interleukin 3 (EC IL-3) is spontaneously released by freshly isolated EC, A 431, and squamous cell carcinoma (SCC) cells. However, both normal EC and A 431 cells produced increased levels of EC IL-3 activity when cultured in the presence of different stimulants, such as phorbol myristate acetate and lipopolysaccharide. The EC IL-3 activity was not inhibited when treated with a monoclonal anti-IL-1 or anti-IL-2-antibody. Biochemical characterization showed that human EC IL-3 has a molecular weight of 17K, elutes of DEAE-ion exchange high-performance liquid chromatography (HPLC) as one major peak at 0.36 M NaCl, and upon HPLC-chromatofocusing exhibits 3 isoelectric points of 7.8, 7.5, and 5.6. Upon reversed-phase HPLC, EC IL-3 activity eluted at about 100% acetonitrile. When highly purified EC IL-3 was labeled with 125I and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a single homogeneous band exhibiting a molecular weight of 17K was seen, which correlated with the IL-3 activity and was free of ETAF/IL-1, IL-2, and interferon activity. These data indicate that human EC synthesize an IL-3-like cytokine which is distinct from ETAF/IL-1, IL-2, and interferon and thereby may participate in the regulation of mast cell activity during inflammatory and fibrotic, as well as hypersensitivity reactions.
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PMID:Human keratinocytes and epidermoid carcinoma cell lines produce a cytokine with interleukin 3-like activity. 243 14

Although mast cells and interferons are both involved in numerous immune and inflammatory responses, little is known about how microenvironmental factors such as interferons (IFNs) influence mast cell function. To study this question, sensitized peritoneal mast cells (greater than 98% purity) obtained from rats infected 4 weeks earlier with the parasite Nippostrongylus brasiliensis were preincubated for 24 hr with rat IFN-alpha/beta in RPMI-1640, then stimulated to degranulate with worm antigens. In the absence of antigen, IFN-alpha/beta had no noticeable effect on histamine release. However, in the presence of antigen, IFN-alpha/beta (150-1500 U/ml) inhibited histamine release in a dose-dependent manner (22.2 +/- 7.5% to 56.3 +/- 6.9%, n = 10). This inhibitory effect was neither heat (56 degrees for 1 hr) nor acid (pH 2 for 18 hr) labile, but was completely blocked by anti-IFN antibodies. In the presence of compound 48/80 (1 microgram/ml) or substance P (5 X 10(-5) M), IFN-alpha/beta was ineffective at modulating histamine release. Histamine release induced by antigen in the presence of the membrane phospholipid phosphatidyl-serine (30 micrograms/ml) was inhibited by IFN in a dose-dependent manner, but maximal inhibition (25.3 +/- 2.7%, n = 10) was reached at a lower concentration of IFN (750 U/ml) than when antigen was used alone. Therefore, rat IFN-alpha/beta appears to inhibit histamine release from rat mast cells in a dose- and stimulus-dependent manner and may do so by reducing the fluidity of the cell membrane.
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PMID:Interferon-alpha/beta inhibits IgE-dependent histamine release from rat mast cells. 246 45

Lymphoid and bone marrow cells from normal and horse serum-immunized mice and lymphoid cells from Nippostrongylus brasiliensis-infected mice were cultured on monolayers of embryonic skin fibroblasts to analyze the factors which regulate the differentiation and proliferation of mast cells in vitro. Our results indicate that T cells can regulate the development of mast cells in vitro by either enhancement or suppression. In cultures of horse serum-immune spleen cells, inducer T cells are required for mast cells to develop. However, in cultures of mesenteric lymph node cells from N. brasiliensis-infected mice, inducer T cells are not required for mast cell development. This suggests that the development of mast cells may occur at discrete interleukin-3 (IL-3)-dependent and IL-3-independent stages. Mast cell precursors in the mesenteric lymph nodes of N. brasiliensis-infected mice may have already been acted on by inducer cells in vivo to become mast cell committed. While IL-3 does not appear to be required for mast cell development, these precursors do require the presence of a connective tissue microenvironment such as embryonic skin. The precursors can be inhibited from development by interferon preparations.
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PMID:Mast cell differentiation in cultures of T cell-depleted mesenteric lymph node cells from Nippostrongylus brasiliensis-infected mice. 296 49

Bone marrow-derived (colony-stimulating factor [CSF]-dependent) diffuse colonies have been shown to include colonies with cytotoxic activity. Such diffuse colonies were expanded for 6-8 weeks in liquid culture medium in the presence of pokeweed mitogen- or concanavalin A-conditioned spleen cell medium (CM). The morphology of the expanded diffuse colony cells (EDCC) was like that of early myelocytic cells. EDCC lost their cytotoxic capacity when expanded, but the cytotoxicity could be reinduced by pretreatment of the colonies with interferon or phorbol ester. Traditional sources of mouse or human CSF such as lung CM, placenta CM and human mononuclear cell CM did not support proliferation of EDCC, whereas partly purified interleukin-3 (IL-3), lacking CSF and IL-2, was stimulatory for EDCC. Thus, the stimulatory factor for EDCC was not CSF but a factor closely related to IL-3. Monoclonal antibodies against T lymphocytes or macrophages did not bind to EDCC. EDCC did not have Fc receptors, but 10% of the cells were positive for a monoclonal anti-Ia antibody. All EDCC were positive for alpha NAE and NASDCI esterases but negative for acid and alkaline phosphatases and peroxidase reactivity; less than 2% of the cells showed metachromatic staining with toluidine. Ultrastructurally, EDCC showed various degrees of cell differentiation but absence of specific cytoplasmatic characteristics such as neutrophilic, eosinophilic, basophilic and mast cell granules. Current work aims to define factors and conditions necessary for the induction of differentiation in these immature monomyelocytic cells.
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PMID:Expanded progeny cells of diffuse cytotoxic bone marrow-derived colonies. 618 13

Purified mouse T lymphocytes were separated into Lyt-2+ and Lyt-2- populations by the procedure of panning, in which a monoclonal rat anti-Lyt-2 antibody and dishes coated with affinity-purified mouse anti-rat Ig antibodies were used. The populations obtained were 95 to 99% pure as determined by immunofluorescence. Graded doses of these T cells were cultured with optimal mitogenic doses of concanavalin A and the 0 to 24 and 24 to 48-hr culture supernatants were collected. The dose-curve assays of the supernatants of Lyt-2+ and Lyt-2- cells showed comparable activity in interleukin 2 (IL 2) and T cell-replacing factor (TRF), assayed on antigen-stimulated culture of T-depleted spleen cells. Limiting dilution assays of IL 2-secreting precursor cells stimulated by Con A showed a high frequency of precursors in both populations, slightly higher among Lyt-2- cells. The supernatants also contained comparable levels of IPA (inducer of plasminogen activator production by the macrophages), MAF (macrophage-activating factor, assayed by induction of their cytolytic function), and MCGF (mast cells growth factor, assayed on a mast cell line). IPA and MAF were not produced with the same kinetics and in the same T cell concentration conditions as IL 2 and TRF. In contrast, interferon was principally produced by the Lyt-2+ cells.
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PMID:Positively selected Lyt-2+ and Lyt-2- mouse T lymphocytes are comparable, after Con A stimulation, in release of IL 2 and of lymphokines acting on B cells, macrophages, and mast cells, but differ in interferon production. 618 45

The recent purification and cloning of T cell-derived growth factors, should lead to rapid progress in delineating their role in the generation of accessory cells and the regulation of their function. The techniques that have allowed detailed in vitro studies of the T-dependent mast cells, should be generally applicable to other bone-marrow-derived cells. Although the T-dependent mast cell (i.e. P cells) of the mouse appear to have a special propensity to persist in vitro and special techniques that promote the emergence of immortalized clones will probably be necessary to grow useful quantities of other cell-types in vitro using PSF, it should prove possible to develop factor-dependent lines of various bone-marrow-derived accessory cells such as dendritic cells and Langerhans cells. The availability of clonal populations will permit analysis of the interaction of factors such as haematopoietic growth factors, interferon, glucocorticoids and other mediators involved in inflammatory reactions such as the prostaglandins and leukotrienes - not only in the regulation of Ia-antigen expression but also in modulation of other accessory cell functions such as the secretion of IL-1 and perhaps ultimately the processing and presentation of antigens.
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PMID:T-cell-lymphokines and the production and function of accessory cells. 644 70

In order to gain insights into the dynamics of mast cell subpopulations in normal and diseased skin, a novel enzyme-histochemical double and triple staining method was employed that allowed the detection of metachromasia (toluidine blue) and the mast cell proteases tryptase and chymase within the same cell. Cryostat sections were used of skin biopsies from the following specimens: normal skin (N = 4), psoriasis (N = 13), atopic eczema (N = 7), lichen planus (N = 6), interferon alpha 2a injection sites (N = 1) of a leukemic infiltrate and corresponding normal skin of the same patient before and after treatment. (i) Equal numbers of tryptase- and chymase-positive mast cells (MCTC) were obtained in all normal and diseased specimens in papillary and reticular dermis, with threefold increases around appendages. (ii) Tryptase-positive mast cells (MCT) were absent in normal skin, but were markedly increased in a disease-specific pattern within the papillary dermis, the inflammatory infiltrate and around appendages. (iii) Marked increases of MCT were also noted at interferon injection sites within the leukemic infiltrate, but not in the normal skin of the same patient. These data suggest that disease-dependent mast cell dynamics involve only MCT in cutaneous inflammation and that MCT numbers are controlled by distinct, disease-specific local tissue factors.
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PMID:Analysis of mast cell subpopulations (MCT, MCTC) in cutaneous inflammation using novel enzyme-histochemical staining techniques. 753 9

Cytokines represent the major factors involved in the communication between T cells, macrophages and other immune cells in the course of an immune response to antigens and infectious agents. A number of studies on mouse and human T helper (Th) clones have recently provided extensive evidence for the existence of different activities exhibited by Th cells (called Th1 and Th2), which was apparently inferred from the profile of cytokine secretion. The Th1-type immune response is generally associated with IgG2a production and the development of cellular immunity, the Th2-type response with IgE production, eosinophils and mast cell production. This review focuses on the role of different cytokines produced by macrophages (especially interferons (IFNs), TNF-alpha, IL-10 and IL-12) or T cells (IFNs, IL-2, IL-4, IL-10, IL-13 and TGF-beta) in macrophage-T cell interactions and the cytokine relevance in the differentiation of Th cells towards the Th1 or Th2 type of immune response. Th1-derived cytokines (IFN-gamma, IL-2, TNF-alpha) favor macrophage activation, whereas the Th2 cytokines (IL-4, IL-10, IL-13) exhibit suppressive activities on macrophage functions. A key role in the differentiation towards the Th1-type response is now attributed to IL-12, a recently described cytokine produced mainly by macrophages. Its production can be upregulated by IFN-gamma and is inhibited by IL-10 and IL-4. All this emphasizes the importance of macrophage-cytokine interactions in determining the type of immune response. This article also aims to review recent data concerning the roles of IFNs alpha/beta (type I) and IFN-gamma (type II) in the regulation of the immune response. While there is much information on the regulatory effects of IFN-gamma (also called "immune IFN") on the immune response, little is so far known of the role of type I IFNs. These cytokines, originally described as simple antiviral substances, are now taken to be important regulators of the immune response. Recent data indicate that these molecules (especially IFNs-alpha) specifically promote the differentiation towards the Th1-type response. The stimulatory effects of IFN-alpha on the generation of the Th1-type response may be involved in its therapeutic effects in some human diseases, including early AIDS, hypereosinophilia and certain tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of interferons and other cytokines in the regulation of the immune response. 753 71


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